EP2921186A1 - Procédé de recuisson de polyéthylène réticulé - Google Patents

Procédé de recuisson de polyéthylène réticulé Download PDF

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Publication number
EP2921186A1
EP2921186A1 EP15159360.5A EP15159360A EP2921186A1 EP 2921186 A1 EP2921186 A1 EP 2921186A1 EP 15159360 A EP15159360 A EP 15159360A EP 2921186 A1 EP2921186 A1 EP 2921186A1
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Prior art keywords
uhmwpe
preform
temperature
set forth
irradiated
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German (de)
English (en)
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EP2921186B1 (fr
Inventor
Lin Song
Daniel E. Lawrynowicz
Kim-phuong Nguyen Le
Kevor Shane Tenhuisen
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Howmedica Osteonics Corp
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Howmedica Osteonics Corp
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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29B—PREPARATION OR PRETREATMENT OF THE MATERIAL TO BE SHAPED; MAKING GRANULES OR PREFORMS; RECOVERY OF PLASTICS OR OTHER CONSTITUENTS OF WASTE MATERIAL CONTAINING PLASTICS
    • B29B13/00—Conditioning or physical treatment of the material to be shaped
    • B29B13/08—Conditioning or physical treatment of the material to be shaped by using wave energy or particle radiation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/16—Macromolecular materials obtained by reactions only involving carbon-to-carbon unsaturated bonds
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29B—PREPARATION OR PRETREATMENT OF THE MATERIAL TO BE SHAPED; MAKING GRANULES OR PREFORMS; RECOVERY OF PLASTICS OR OTHER CONSTITUENTS OF WASTE MATERIAL CONTAINING PLASTICS
    • B29B11/00—Making preforms
    • B29B11/14—Making preforms characterised by structure or composition
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29B—PREPARATION OR PRETREATMENT OF THE MATERIAL TO BE SHAPED; MAKING GRANULES OR PREFORMS; RECOVERY OF PLASTICS OR OTHER CONSTITUENTS OF WASTE MATERIAL CONTAINING PLASTICS
    • B29B13/00—Conditioning or physical treatment of the material to be shaped
    • B29B13/02—Conditioning or physical treatment of the material to be shaped by heating
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29B—PREPARATION OR PRETREATMENT OF THE MATERIAL TO BE SHAPED; MAKING GRANULES OR PREFORMS; RECOVERY OF PLASTICS OR OTHER CONSTITUENTS OF WASTE MATERIAL CONTAINING PLASTICS
    • B29B13/00—Conditioning or physical treatment of the material to be shaped
    • B29B13/04—Conditioning or physical treatment of the material to be shaped by cooling
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29B—PREPARATION OR PRETREATMENT OF THE MATERIAL TO BE SHAPED; MAKING GRANULES OR PREFORMS; RECOVERY OF PLASTICS OR OTHER CONSTITUENTS OF WASTE MATERIAL CONTAINING PLASTICS
    • B29B15/00—Pretreatment of the material to be shaped, not covered by groups B29B7/00 - B29B13/00
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C49/00—Blow-moulding, i.e. blowing a preform or parison to a desired shape within a mould; Apparatus therefor
    • B29C49/071—Preforms or parisons characterised by their configuration, e.g. geometry, dimensions or physical properties
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C71/00—After-treatment of articles without altering their shape; Apparatus therefor
    • B29C71/04—After-treatment of articles without altering their shape; Apparatus therefor by wave energy or particle radiation, e.g. for curing or vulcanising preformed articles
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C35/00—Heating, cooling or curing, e.g. crosslinking or vulcanising; Apparatus therefor
    • B29C35/02—Heating or curing, e.g. crosslinking or vulcanizing during moulding, e.g. in a mould
    • B29C35/08—Heating or curing, e.g. crosslinking or vulcanizing during moulding, e.g. in a mould by wave energy or particle radiation
    • B29C35/0805—Heating or curing, e.g. crosslinking or vulcanizing during moulding, e.g. in a mould by wave energy or particle radiation using electromagnetic radiation
    • B29C2035/0844—Heating or curing, e.g. crosslinking or vulcanizing during moulding, e.g. in a mould by wave energy or particle radiation using electromagnetic radiation using X-ray
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C35/00—Heating, cooling or curing, e.g. crosslinking or vulcanising; Apparatus therefor
    • B29C35/02—Heating or curing, e.g. crosslinking or vulcanizing during moulding, e.g. in a mould
    • B29C35/08—Heating or curing, e.g. crosslinking or vulcanizing during moulding, e.g. in a mould by wave energy or particle radiation
    • B29C35/0805—Heating or curing, e.g. crosslinking or vulcanizing during moulding, e.g. in a mould by wave energy or particle radiation using electromagnetic radiation
    • B29C2035/085—Heating or curing, e.g. crosslinking or vulcanizing during moulding, e.g. in a mould by wave energy or particle radiation using electromagnetic radiation using gamma-ray
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C35/00—Heating, cooling or curing, e.g. crosslinking or vulcanising; Apparatus therefor
    • B29C35/02—Heating or curing, e.g. crosslinking or vulcanizing during moulding, e.g. in a mould
    • B29C35/08—Heating or curing, e.g. crosslinking or vulcanizing during moulding, e.g. in a mould by wave energy or particle radiation
    • B29C35/0866—Heating or curing, e.g. crosslinking or vulcanizing during moulding, e.g. in a mould by wave energy or particle radiation using particle radiation
    • B29C2035/0877—Heating or curing, e.g. crosslinking or vulcanizing during moulding, e.g. in a mould by wave energy or particle radiation using particle radiation using electron radiation, e.g. beta-rays
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C71/00—After-treatment of articles without altering their shape; Apparatus therefor
    • B29C71/02—Thermal after-treatment
    • B29C2071/022—Annealing
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C2949/00—Indexing scheme relating to blow-moulding
    • B29C2949/07—Preforms or parisons characterised by their configuration
    • B29C2949/0715—Preforms or parisons characterised by their configuration the preform having one end closed
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C35/00—Heating, cooling or curing, e.g. crosslinking or vulcanising; Apparatus therefor
    • B29C35/02—Heating or curing, e.g. crosslinking or vulcanizing during moulding, e.g. in a mould
    • B29C35/08—Heating or curing, e.g. crosslinking or vulcanizing during moulding, e.g. in a mould by wave energy or particle radiation
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C43/00—Compression moulding, i.e. applying external pressure to flow the moulding material; Apparatus therefor
    • B29C43/003—Compression moulding, i.e. applying external pressure to flow the moulding material; Apparatus therefor characterised by the choice of material
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C43/00—Compression moulding, i.e. applying external pressure to flow the moulding material; Apparatus therefor
    • B29C43/02—Compression moulding, i.e. applying external pressure to flow the moulding material; Apparatus therefor of articles of definite length, i.e. discrete articles
    • B29C43/10—Isostatic pressing, i.e. using non-rigid pressure-exerting members against rigid parts or dies
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29K—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES B29B, B29C OR B29D, RELATING TO MOULDING MATERIALS OR TO MATERIALS FOR MOULDS, REINFORCEMENTS, FILLERS OR PREFORMED PARTS, e.g. INSERTS
    • B29K2023/00—Use of polyalkenes or derivatives thereof as moulding material
    • B29K2023/04—Polymers of ethylene
    • B29K2023/06—PE, i.e. polyethylene
    • B29K2023/0658—PE, i.e. polyethylene characterised by its molecular weight
    • B29K2023/0683—UHMWPE, i.e. ultra high molecular weight polyethylene
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29K—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES B29B, B29C OR B29D, RELATING TO MOULDING MATERIALS OR TO MATERIALS FOR MOULDS, REINFORCEMENTS, FILLERS OR PREFORMED PARTS, e.g. INSERTS
    • B29K2105/00—Condition, form or state of moulded material or of the material to be shaped
    • B29K2105/25—Solid
    • B29K2105/253—Preform

Definitions

  • This invention relates to medical implants formed of a polymeric material such as ultra-high molecular weight polyethylene (UHMWPE), with superior properties such as, superior oxidation and wear resistance produced by a sequential irradiation and annealing process, further including a hot isostatic pressing step performed on a UHMWPE preform.
  • a preform may be an UHMWPE rod, bar, plate or portion thereof consolidated from an UHMWPE resin.
  • Ultra-high molecular weight polyethylene is widely used for articulation surfaces in artificial knee, hip, and other joint replacements.
  • Ultra-high molecular weight polyethylene has been defined as those linear polyethylenes which have a relative viscosity of 2.3 or greater at a solution concentration of 0.05% at 135°C in decahydronaphthalene.
  • the nominal weight - average molecular weight is at least 400,000 and up to 10,000,000 and usually from three to six million.
  • the manufacturing process begins with the polymer being supplied as fine resin powder which is consolidated into various forms, such as rods, bars and slabs, using ram extrusion injection molding or compression molding. Afterwards, the consolidated rods or slabs are machined into the final shape of the orthopedic implant components. Alternatively, the component can be produced by compression or injection molding of the UHMWPE resin powder.
  • the high energy beam causes generation of free radicals in polymers during radiation. It has also been recognized that the amount or number of free radicals generated is dependent upon the radiation dose received by the polymers and that the distribution of free radicals in the polymeric implant depends upon the geometry of the component, the type of polymer, the dose rate, and the type of radiation beam.
  • the generation of free radicals can be described by the following reaction (which uses polyolefin and gamma ray irradiation for illustration): *(through C-C chain scission or C-H scission)
  • reaction 7 hydroperoxides (rOOH and POOH) formed in reactions 3 and 5 will slowly break down as shown in reaction 7 to initiate post-radiation degradation.
  • Reactions 8 and 9 represent termination steps of free radicals to form ester or carbon-carbon cross-links.
  • the extent of reactions 8 and 9 in relation to reactions 2 through 7 may vary.
  • irradiated UHMWPE a value of 0.3 for the ratio of chain scission to cross-linking has been obtained, indicating that even though cross-linking is a dominant mechanism, a significant amount of chain scission occurs in irradiated polyethylene.
  • the primary free radicals r ⁇ or secondary free radicals P ⁇ can only react with other neighboring free radicals to form carbon-carbon cross-links, according to reactions 10 through 12 below. If all the free radicals react through reactions 10 through 12, there will be no chain scission and there will be no molecular weight degradation. Furthermore, the extent of cross-linking is increased over the original polymer prior to irradiation. On the other hand, if not all the free radicals formed are combined through reactions 10, 11 and 12, then some free radicals will remain in the plastic component.
  • UHMWPE is commonly used to make prosthetic joints such as artificial hip joints.
  • tissue necrosis and interface osteolysis may occur in response to UHMWPE wear debris.
  • wear of acetabular cups of UHMWPE in artificial hip joints may introduce microscopic wear particles into the surrounding tissues.
  • ultrahigh molecular weight polyethylene can be cross-linked by irradiation with high energy radiation, for example gamma radiation, in an inert atmosphere or vacuum. Exposure of UHMWPE to gamma irradiation induces a number of free-radical reactions in the polymer. One of these is cross-linking. This cross-linking creates a 3-dimensional network in the polymer which renders it more resistant to adhesive wear in multiple directions.
  • the free radicals formed upon irradiation of UHMWPE can also participate in oxidation which reduces the molecular weight of the polymer via chain scission, leading to degradation of physical properties, embrittlement and a significant increase in wear rate.
  • the free radicals are very long-lived (greater than eight years), so that oxidation continues over a very long period of time resulting in an increase in the wear rate as a result of oxidation over the life of the implant.
  • Hyon et al. U.S. Patent No. 6,168,626 relates to a process for forming oriented UHMWPE materials for use in artificial joints by irradiating with low doses of high-energy radiation in an inert gas or vacuum to cross-link the material to a low degree, heating the irradiated material to a temperature at which compressive deformation is possible, preferably to a temperature near the melting point or higher, and performing compressive deformation followed by cooling and solidifying the material.
  • the oriented UHMWPE materials have improved wear resistance. Medical implants may be machined from the oriented materials or molded directly during the compressive deformation step. The anisotropic nature of the oriented materials may render them susceptible to deformation after machining into implants.
  • Salovey et al. U.S. Patent No. 6,228,900 the teachings of which are incorporated by reference, relates to a method for enhancing the wear-resistance of polymers, including UHMWPE, by cross-linking them via irradiation in the melt.
  • U.S. Patent No. 6,316,158 relates to a process for treating UHMWPE using irradiation followed by thermally treating the polyethylene at a temperature greater than 150°C to recombine cross-links and eliminate free radicals.
  • UHMWPE powders being heated and compressed into a homogeneously melted crystallized morphology with no grain memory of the UHMWPE powder particles and with enhanced modulus and strength.
  • U.S. Patent No. 5,037,928 relates to a prescribed heating and cooling process for preparing a UHMWPE exhibiting a combination of properties including a creep resistance of less than 1% (under exposure to a temperature of 23°C and a relative humidity of 50% for 24 hours under a compression of 1000 psi) without sacrificing tensile and flexural properties.
  • Patent Application GB 2 180 815 A relates to a packaging method where a medical device which is sealed in a sterile bag, after radiation/sterilization, is hermetically sealed in a wrapping member of oxygen-impermeable material together with a deoxidizing agent for prevention of post-irradiation oxidation.
  • U.S. Patent No. 5,153,039 relates to a high density polyethylene article with oxygen barrier properties.
  • U.S. Patent No. 5,160,464 relates to a vacuum polymer irradiation process.
  • the present invention relates to a method for providing a polymeric material, such as UHMWPE, with mechanical properties such as, superior oxidation resistance, mechanical strength and wear properties.
  • UHMWPE will be used as an example to describe the invention.
  • all the theories and processes described hereafter should also apply to other polymeric materials such as polypropylene, high density polyethylene, polyhydrocarbons, polyester, nylon, polyurethane, polycarbonates and poly(methylmethacrylate) unless otherwise stated.
  • the method involves using a series of relatively low doses of radiation with an annealing process after each dose, further comprising a hot isostatic pressing step performed before, after or between the sequential irradiation and cross-linking steps.
  • UHMWPE polymer is very stable and has very good resistance to aggressive media except for strong oxidizing acids.
  • free radicals are formed which cause UHMWPE to become activated for chemical reactions and physical changes.
  • Possible chemical reactions include reacting with oxygen, water, body fluids, and other chemical compounds while physical changes include density, crystallinity, color, and other physical properties.
  • the sequential radiation and annealing process greatly improves the physical properties of UHMWPE when compared to applying the same total radiation dose in one step. Furthermore, this process does not employ stabilizers, antioxidants, or any other chemical compounds which may have potentially adverse effects in biomedical or orthopedic applications.
  • An orthopedic preformed material such as a rod, bar or compression molded sheet or plate for the subsequent production of a medical implant such as an acetabular or tibial implant with improved wear resistance is made from a polyethylene material cross-linked at least twice by irradiation and thermally treated by annealing after each irradiation.
  • the material is cross-linked by a total radiation dose of from about 2 MRads to 100 MRads and preferably between 5 MRads and 10 MRads.
  • the incremental dose for each irradiation is between about 2 MRads and about 5 MRads.
  • the weight average molecular weight of the material is over 400,000.
  • the annealing takes place at a temperature greater than 25°C, preferably between 110°C and 135°C but less than the melting point. Generally, the annealing takes place for a time and temperature selected to be at least equivalent to heating the irradiated material at 50°C for 144 hours as defined by Arrenhius' equation 14. The material is heated for at least about 4 hours and then cooled to room temperature for the subsequent irradiation in the series.
  • the crystallinity will fluctuate between 55% and 60% (instead of 55-65%) and hence both the amount of chain-scission and residual free-radical concentration can be significantly reduced.
  • the polyethylene of the present invention may be in the form of a preformed rod such as an extruded rod or sheet with a subsequent production of a medical implant with improved wear resistance.
  • the preformed rod or sheet is cross-linked at least twice by irradiation and thermally treated by annealing after each radiation.
  • the incremental dose for each radiation is preferably between about 2 and 5 MRads with the total dose between 2 and 100 MRads and preferably between 5 and 10 MRads.
  • the preformed material is annealed either in air or in an inert atmosphere at a temperature of greater than 25°C and preferably less than 135°C or the melting point.
  • the annealing takes place for a time and temperature selected to be at least equivalent to heating the irradiated material at 50°C for 144 hours as defined by Arrenhius' equation (14).
  • each heat treatment lasts for at least 4 hours and preferably about 8 hours.
  • the preformed rod, bar, plate or sheet is not isostatically pressed as described above to further improve mechanical properties such as the IZOD impact strength.
  • the preformed polyethylene material is then machined into a medical implant or other device. If the irradiation process occurred in air, then the entire outer skin to about 2 mm deep is removed from the preform prior to machining the medical implant or other device. If the process was done in a vacuum or an inner atmosphere such as nitrogen, then the outer skin may be retained.
  • UHMWPE ultra-high molecular weight polyethylene
  • This first consolidation step may be done by compression molding or extrusion (HIP).
  • HIP compression molding or extrusion
  • the consolidated UHMWPE is hot isostatically pressed at a temperature between 130°C and 190°C at a pressure up to 30,000 psi. This is done prior to irradiation as a second consolidation step.
  • the advantage to performing the second consolidation prior to irradiation is that the polymer chains are not cross-linked, therefore more mobile, therefore more easily consolidated.
  • the hot isostatic pressing of the preform preferably occurs prior to irradiating the UHMWPE preform.
  • the hot isostatic pressing preferably occurs at a temperature between 150°C and 170°C.
  • the UHMWPE perform may be consolidated by a method selected from the group consisting of direct compression molding, extrusion and injection molding.
  • the UHMWPE perform is irradiated at least two times and heated after each irradiation to below the melting temperature followed by cooling after each heating.
  • the cooling of the preform to or below 50°C is done at a rate equal to or less than 2°C/min. More preferably the rate is less than 0.07°C/min.
  • the heating temperature after irradiation for the UHMPWE is between 110°C and 130°C.
  • UHMWPE ultra-high molecular weight polyethylene
  • a preform such as a sheet, rod or block
  • the UHMWPE perform is irradiated in a solid state at a radiation dose of 2 to 10 MRAD.
  • a hot isostatic pressing of the UHMWPE preform then takes place at a temperature between 130°C and 190°C and a pressure greater than about 500 psi for at least about 4 hours.
  • the irradiated preform is heated to a temperature of about 110°C to about 130°C for at least about 2 hours.
  • the heated preform is cooled to a temperature to or below 50° prior to making a medical implant from the UHMWPE.
  • the hot isostatic pressing of the preform preferably is at a temperature between 150°C and 170°C.
  • the hot isostatic pressing of the preform is preferably at a pressure between 2000 psi and 30,000 psi.
  • the UHMWPE perform may be first consolidated by a method selected from the group consisting of direct compression molding, extrusion and injection molding.
  • Preferably the ot isostatic pressing second consolidation is done prior to irradiating.
  • the UHMWPE perform is preferably irradiated at least two times and heated between 110°C and 130°C for about eight hours after each irradiation followed by cooling after each heating.
  • the cooling is to or below 50°C and is done at a rate equal to or less than 2°C/min.
  • the rate may be less than 0.07°C/min.
  • Aspects of the invention may be achieved by a method for making an ultra-high molecular weight polyethylene (UHMWPE) medical implant including hot isostatically pressing (Hipping) a UHMWPE preform at a temperature between 130°C and 190°C at a pressure up to 30,000 psi. After the HIP process, the UHMWPE preform is irradiated at least three times to a total dose of 5 to 10 MRad.
  • UHMWPE ultra-high molecular weight polyethylene
  • the irradiated preform is heated after each irradiation for at least about 8 hours at a temperature from about 110°C to 130°C followed by cooling the UHMWPE preform after each irradiation and heating.
  • the hot isostatic pressing of the preform occurs a single time prior to irradiating the UHMWPE preform.
  • the hot isostatic pressing preferably occurs at a temperature between 150°C and 170°C.
  • end-results of these methods are reduced chain-scission and free-radical concentration are improved mechanical properties, improved oxidation resistance and enhanced wear resistance.
  • This invention provides a method for improving the impact strength of a polymer by using a Hot Isostatic Pressing step before or after crosslinking using radiation and then thermally treating the resulting polymer.
  • the method of the invention utilizes at least two separate irradiations for crosslinking a polymer followed by a like number of thermal treatments to decrease the free radicals to produce either a treated fully formed or a preformed polymeric composition.
  • preformed polymeric composition or "preform” means that the polymeric composition is not in a final desired shape or form (i.e., not a final product).
  • the at least two irradiations and thermal treatments of the polymer could be performed on a pre-acetabular cup shape, such as when the preformed polymeric composition is in the form of a solid bar or block.
  • the process of the present invention could be applied to a fully formed implant if the process is done with the implant in an oxygen reduced atmosphere.
  • the wear resistance of a polymer is improved by crosslinking.
  • the crosslinking can be achieved by various methods known in the art, for example, by irradiation from a gamma radiation source or from an electron beam, or from an X-ray radiation, or by photo crosslinking.
  • the preferred method for crosslinking the polymer is by gamma irradiation.
  • the polymer is preferably crosslinked in the form of an extruded bar or molded block.
  • the crosslinked polymer is subjected to thermal or heat treatment such as by annealing (i.e. heated above at or below the melting temperature of the crosslinked polymer about 135°C) to produce the preformed polymeric composition.
  • annealing i.e. heated above at or below the melting temperature of the crosslinked polymer about 135°C
  • the heat treatment may be above the melt (between approximately 130° and 190°C).
  • High molecular weight (HMW) and ultra-high molecular weight (UHMW) polymers are preferred, such as HMW polyethylene (HMWPE), UHMW polyethylene (UHMWPE), and UHMW polypropylene.
  • HMW polymers have molecular weights ranging from about 10 5 grams per mole to just below 10 6 .
  • UHMW polymers have molecular weights equal to or higher than 10 6 grams per mole, preferably from 10 6 to about 10 7 .
  • the polymers are generally between about 400,000 grams per mole to about 10,000,000 and are preferably polyolefinic materials.
  • UHMWPE is the most preferred polymer as it is known for these properties and is currently widely used to make acetabular cups for total hip prostheses and components of other joint replacements.
  • UHMWPE are those having molecular weight ranging from about 1 to 8x10 6 grams per mole, examples of which are: GUR 1150 or 1050 (Hoechst-Celanese Corporation, League City, Tex.) with a weight average molecular weight of 5 to 6x10 6 grams per mole; GUR 1130 with a weight average molecular weight of 3 to 4x10 6 ; GUR 1120 or 1020 with a weight average molecular weight of 3 to 4x10 6 ; RCH 1000 (Hoechst-Celanese Corp.) with a weight average of molecular weight of 4x10 6 and HiFax 1900 of 2 to 4x10 6 (HiMont, Elkton, Md.). Historically, companies which make
  • the degree of crystallinity can be determined using methods known in the art, e.g. by differential scanning calorimetry (DSC), which is generally used to assess the crystallinity and melting behavior of a polymer.
  • DSC differential scanning calorimetry
  • Wide-angle X-ray scattering from the resulting polymer can also be used to further confirm the degree of crystallinity of the polymer, e.g. as described in Spruiell, J.E., & Clark, E.S., in "Methods of Experimental-Physics,” L. Marton & C. Marton, Eds., Vol. 16, Part B, Academic Press, New York (1980 ).
  • Other methods for determining the degree of crystallinity of the resulting polymer may include Fourier Transform Infrared Spectroscopy (FTIR), e.g., as described in " Fourier Transform Infrared Spectroscopy And Its Application To Polymeric Materials," John Wiley and Sons, New York, U.S.A.
  • FTIR Fourier Transform Infrared Spectroscopy
  • the preformed polymeric composition may be shaped, e.g., machined, into the appropriate implants using methods known in the art.
  • the shaping process such as machining, removing the oxidized surface of the composition.
  • the preformed polymeric compositions of the present invention can be used in any situation where a polymer, especially UHMWPE, is called for, but especially in situations where high wear resistance is desired. More particularly, these preformed polymeric compositions are useful for making implants.
  • an important aspect of this invention presents implants that are made with the above preformed polymeric compositions or according to the methods presented herein.
  • the implants are produced from preformed polymeric composition made of UHMWPE irradiated and crosslinked at least twice each time followed by annealing and then removing the oxidized surface layer and then fabricating into a final shape.
  • the preformed polymeric composition of the present invention can be used to make the acetabular cup, or the insert or liner of the cup, or trunnion bearings (e.g. between the modular head and the hip stem).
  • the tibial plateau (femoro-tibial articulation), the patellar button (patello-femoral articulation), and/or other bearing components, depending on the design of the artificial knee joint.
  • the process can be used in the glenoid component.
  • the preformed polymeric composition can be used to make the talar surface (tibiotalar articulation) and other bearing components.
  • the preformed polymeric composition can be used to make the radio-humeral joint, ulno-humeral joint, and other bearing components.
  • the preformed polymeric composition can be used to make intervertebral disk replacement and facet joint replacement.
  • the preformed polymeric composition can also be made into temporo-mandibular joint (jaw) and finger joints.
  • jaw temporo-mandibular joint
  • finger joints The above are by way of example, and are not meant to be limiting.
  • Free radicals generated during an irradiation step should be reduced to an acceptable level by annealing before exposure to oxygen.
  • the portion of the material from which the implant is made contains free radicals and if it is exposed to air or other oxidants after the manufacturing process, oxidation will occur.
  • an elevated temperature not only increases the reaction rate constants, k 1 and k 2 , but also helps free radicals r ⁇ and P ⁇ to migrate in the plastic matrix to meet other neighboring free radicals for cross-linking reactions.
  • the desired elevated temperature is between room temperature to below the melting point of the polymer.
  • this temperature range is between about 25°C and about 140°C. It is to be noted that the higher the temperature used, the shorter the time period needed to combine free radicals.
  • the formed UHMWPE often contains residual (internal) stress caused by incomplete relaxation during the cooling process, which is the last step of the forming process.
  • the annealing process described herein will also help to eliminate or reduce the residual stress. A residual stress contained in a plastic matrix can cause dimensional instability and is in general undesirable.
  • the sequential irradiation followed by sequential annealing after each irradiation is performed in air on a preform such as an compressed block, bar or compression molded sheet made from polyethylene and preferably UHMWPE.
  • a preform such as an compressed block, bar or compression molded sheet made from polyethylene and preferably UHMWPE.
  • the final sequential annealing must take place prior to the bulk material of the final part or implant being exposed to air. Normally, it takes at least seven days for atmospheric oxygen to diffuse through the outer layer of polyethylene and deeply enough into rod, bar or sheet to effect the bulk polyethylene forming the final part. Therefore, the last annealing in the sequence preferably should take place prior to the time required for the oxygen to diffuse deeply into the rod.
  • the more material which must be machined off to reach the finished part the longer one can wait for the completion of the sequential irradiation and annealing process.
  • the polymeric component is preferably packaged in an air tight package in an oxidant-free atmosphere, i.e. less than 1% volume by volume of oxygen.
  • an oxidant-free atmosphere i.e. less than 1% volume by volume of oxygen.
  • all air and moisture must be removed from the package prior to the sealing step.
  • Machines to accomplish this are commercially available, such as from Orics Industries Inc., College Point, New York, which flush the package with a chosen inert gas, vacuum the container, flush the container for the second time, and then heat seal the container with a lid. In general, less than 0.5% (volume by volume) oxygen concentration can be obtained consistently.
  • oxidant impermeable (air tight) packaging material is polyethylene terephthalate (PET).
  • PET polyethylene terephthalate
  • Other examples of oxidant impermeable packaging material is poly(ethylene vinyl alcohol) and aluminum foil, whose oxygen and water vapor transmission rates are essentially zero. All these materials are commercially available.
  • oxidant impermeable packaging material utilize a layer structure to form a composite material with superior oxygen and moisture barrier properties.
  • An example of this type is a layered composite comprised of polypropylene/poly (ethylene vinyl alcohol)/polypropylene.
  • the heat treatment or annealing step should be performed while the implant is out of contact with oxygen or in an inert atmosphere and at an elevated temperature to cause free radicals to form cross-links without oxidation. If proper packaging materials and processes are used and oxidant transmission rates are minimal, then the oxidant-free atmosphere can be maintained in the package and a regular oven with air circulation can be used for heat treatment after sterilization. To absolutely ensure that no oxidants leak into the package, the oven may be operated under a vacuum or purged with an inert gas. In general, if a higher temperature is used, a shorter time period is required to achieve a prescribed level of oxidation resistance and cross-linking.
  • the method of the present invention uses sequential thermal treatment under pressure (HIPing) to make a homogenized, consolidated UHMWPE for medical implants.
  • HIPing sequential thermal treatment under pressure
  • the sequential thermal treatment consists of a low temperature melting, ranging between 130° C and 190° C, preferably 150-170° C, for 4-10 hours, preferably 8 hours at or a below melting temperature annealing at 130° C for 2-10 hours, preferably 8 hours. Either treatment is followed by cooling to or below 50° C at a rate of equal to or less than 2° C/min, preferably less than 0.07° C/min. This thermal treatment is done while the preform is under pressure in argon.
  • the low temperature melting decrystallizes the consolidation polyethylene and eliminates the non-uniformity of the crystalline microstructure generated during consolidation.
  • the subsequent annealing with the controlled cooling provides an optimal environment for polyethylene molecules to recrystallize to achieve ideal physical and mechanical properties.
  • thermal and pressure treatments discussed above could be applied to any consolidated UHMWPE preform, the consolidation method including but not limited to, compression molding, extrusion, injection molding, and direct compression molding.
  • the thermal and pressure treatment could be conducted in an oven or in a pressurized vessel.
  • the pressure applied should be no more than 30,000 psi, preferably below 2,000 psi, but above 500 psi.
  • the thermal treatment could be applied to non-cross-linked UHMWPE or cross-linked UHMWPE.
  • HIPing Matrix Starting material: virgin and sequentially cross-linked PE blocks followed by hot isostatic pressing as per Table I samples 1-12 followed by sequential cross-linking as in Example I
  • Table II shows the results for seven test samples (1, 3, 4, 6, 7 and 9) which best illustrate the improved impact strengths of the method of the present invention. A graph of the results are shown in Fig. 1 .
  • Table II (Summary of seven samples from Table I) Sequentially cross-linked (GUR 1020) Sample ID Heating Rate (°C/Holding Temp (°C) Holding Pressure (PSI) Holding Time (hrs) Cooling Izod Strength Izod Stdev Before-HIPing Izod 1 (30,000 psi RT) - 0 30000 8 Immediate Release 58 0.7 58 3 (15,000 psi anneal) - 130 15000 8 Immediate Release 57 0.7 58 4 (20,000 psi remelt) - 170 2000 8 Immediate Release 71 1.2 58 6 (2,000 psi, anneal) 5 130 2000 8 0.07°C/min from 130°C to 75°C under pressure 56 0.7 57 7 (2,000 psi,
  • Ultra-high molecular weight polyethylene preform from a compression molded block, is hot isostatically pressed at a pressure of 2000 psi and a temperature of 170°C for 8 hours and then cooled at a rate of 0.07°C/min after irradiated sequentially for a sufficient time for an accumulated incremental dose of between 2 and 5 (MRads) (20 to 50 kGy).
  • MRads 2 and 5
  • the block is annealed in air preferably at a temperature below its melting point, preferably at less than 135°C and more preferably between 110°C and 130°C. The block is then allowed to cool to room temperature.
  • the irradiation and annealing steps are repeated two or more times so that the total radiation dose is between 4 and 15 MRads (50 to 150 kGy).
  • the block is irradiated for a total dose of 3 MRad and then annealed at 130°C for 24 hours, allowed to cool to room temperature and sit for 3 days and then reirradiated for a dose of 3.0 MRads (a total dose of 6 MRads) again annealed at 130°C for 24 hours, allowed to cool at room temperature and sit for an additional 3 days and then irradiated a third time with a 3.0 MRad dose (for a total of 9 MRads) and again annealed at 130°C for 24 hours.
  • Compression molded GUR1020 was thermal treated at 150° C for 8 hours before the first irradiation step of the sequential cross-linking and then sequentially irradiated and annealed.
  • the Izod impact strength and tensile properties were measured.
  • the Izod impact strength of thermal treated material did not differ significantly from the non-thermal treated material before cross-linking.
  • the Izod impact strength of thermal treated and sequentially cross-linked and annealed material increased while the tensile properties remained similar.
  • the above example can also be applied to compression molded sheet with, for example, a tibial component being manufactured out of the sequentially irradiated and annealed material. What is important is that a two-step consolidation is applied.
  • the first consolidation is from the GUR 1020 resin to form a rod, bar or plate.
  • the second consolidation is a hot isostatic pressing before or after irradiation and annealing or remelting.

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AU2015201384B2 (en) 2016-11-10

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